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Concern over animal molecule in drugs

Modern drugs used to treat serious diseases contain an animal molecule that can harm the health of some patients, it was claimed.

The non-human sugar is also present in meat and could help explain dietary associations with heart disease and cancer, say scientists.

Sialic acids are found in all mammals and coat the surfaces of cells, allowing them to interact with their companions and the surrounding environment.

At the same time the sugars are targets for infectious diseases such as influenza, malaria and cholera.

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Humans lack one type of sialic acid that is found in many other mammals, including our close relatives chimpanzees and gorillas.

When the animal version, known as Neu5Gc, finds its way into the human body it triggers an immune response that can have a damaging inflammatory effect in some individuals, said the researchers.

The US scientists found that many modern biotech drugs derived from animal sources - some of which are actually used to treat inflammatory disorders - are contaminated with the sugar.

"It's reasonable to suggest that for some patients who have problems with some drugs, this may be part of the reason why," said Professor Ajit Varki, who led the research published in the journal Nature Biotechnology.

Different species have evolved different kinds of sialic acids.

In mammals, there are two major types, Neu5Gc and Neu5Ac which differ by just one oxygen atom.

Humans only have the "Ac" version, whereas other mammals including chimpanzees also have the "Gc" variety.

The change in humans is thought to have occurred two or three million years ago as a result of natural selection, possibly driven by an infectious disease such as malaria.

Prof Varki, from the University of California at San Diego (UCSD), said: "Sialic acids are required for survival, but they're also used to attack you. They are crucial for things like brain plasticity and kidney function, but lots of pathogens (harmful agents) attach to them, and some even coat themselves with these sugars to avoid detection.

"In evolutionary terms, if you have sialic acid, you're going to be attacked. But if you don't have it, you're going to die."

Previously it was believed that healthy human immune systems were untroubled by non-human sialic acid.

"Now we know that to be untrue," Prof Varki added. "It's part of our diet, and especially abundant in red meat. We all develop antibodies to Neu5Gc, but this immune response varies greatly in people. Meanwhile, Neu5Gc from animal foods can get incorporated into the human body.

"For most people, this may not be a problem. But for some, the immune response to incorporated Neu5Gc may exacerbate a chronic inflammation process. This isn't the cause of any disease or condition, but we believe it might be akin to adding fuel to an existing fire."

The immune response generated by Neu5Gc may partly explain associations between certain foods and diseases linked to inflammation, including cancer and heart disorders, said Prof Varki. These diseases are known to be rare in other primates.

The San Diego scientists studied several therapeutic drugs currently in clinical use and discovered non-human sialic acid in almost all of them.

They also found that anti-Neu5Gc antibodies from healthy humans interacted with a cancer drug containing the sugar.

Mice engineered to lack Neu5Gc produced the same antibodies when injected with the drug.

The same effects were not seen with an otherwise similar drug which happened to be virtually free of the animal sialic acid.

Neu5Gc contamination of modern biotech drugs based on antibodies, clotting factors or hormones, is unavoidable because the medicines are derived from animal cells, tissues or blood serum, said the researchers.

However, the scientists believe they have come up with a simple solution: add human sialic acid to the drug-manufacturing process.

The human "Ac" sugar competes with the "Gc" variant making it less likely for the animal version to appear in the final product.